title: Basic fibroblast growth factor increases constitutive nitric oxide synthase during healing of rat gastric ulcers.
abstract: The purpose of this study was to clarify the effect of basic fibroblast growth factor (bFGF) on nitric oxide (NO) synthesis during healing of rat gastric ulcers. After experimental gastric ulcers were induced by acetic acid, rats were treated with vehicle, recombinant human bFGF (CS23, 10 micrograms/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg), an NO synthase (NOS) inhibitor, through an orogastric tube twice daily for 3 days or 1 week. CS23 significantly reduced ulcer size, and L-NAME significantly delayed healing compared with the vehicle group and significantly inhibited the efficacy of CS23. Although constitutive NOS (cNOS) activity significantly decreased and inducible NOS (iNOS) activity significantly increased in the vehicle group, CS23 significantly inhibited these changes. cNOS immunoreactivity on the vessels and neurons disappeared in the vehicle group, and newly formed vessels as well as neurons were observed with positive endothelial and neuronal NOS immunoreactivity in the CS23-treated group. External administration of bFGF accelerated ulcer healing, with recovery of NO synthesis in both endothelial cells and neurons. These observations suggested that increased NO synthesis with angiogenesis and reinnervation has a beneficial effect on gastric ulcer healing.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Akiba
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Oda
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D019342:Acetic Acid; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester